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The American Journal of Managed Care Dec 2017This activity will update pharmacists and other healthcare professionals on current treatments for pseudobulbar affect (PBA). Points of discussion will focus on the... (Review)
Review
This activity will update pharmacists and other healthcare professionals on current treatments for pseudobulbar affect (PBA). Points of discussion will focus on the off-label therapies traditionally used to treat PBA, the FDA-approved combination drug product with PBA as an indication, and managed care aspects of treating PBA.
Topics: Antidepressive Agents, Tricyclic; Drug Approval; Drug Therapy; Drugs, Investigational; Female; Humans; Male; Medication Therapy Management; Patient Safety; Pseudobulbar Palsy; Risk Assessment; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 29297657
DOI: No ID Found -
Journal of Neural Transmission (Vienna,... Apr 2023Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by early postural instability and falls, oculomotor dysfunction (vertical supranuclear... (Review)
Review
Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by early postural instability and falls, oculomotor dysfunction (vertical supranuclear gaze palsy), parkinsonism with poor response to levodopa, pseudobulbar palsy, and cognitive impairment. This four-repeat tauopathy is morphologically featured by accumulation of tau protein in neurons and glia causing neuronal loss and gliosis in the extrapyramidal system associated with cortical atrophy and white matter lesions. Cognitive impairment being frequent in PSP and more severe than in multiple system atrophy and Parkinson disease, is dominated by executive dysfunction, with milder difficulties in memory, and visuo-spatial and naming dysfunctions. Showing longitudinal decline, it has been related to a variety of pathogenic mechanisms associated with the underlying neurodegenerative process, such as involvement of cholinergic and muscarinergic dysfunctions, and striking tau pathology in frontal and temporal cortical regions associated with reduced synaptic density. Altered striatofrontal, fronto-cerebellar, parahippocampal, and multiple subcortical structures, as well as widespread white matter lesions causing extensive connectivity disruptions in cortico-subcortical and cortico-brainstem connections, support the concept that PSP is a brain network disruption disorder. The pathophysiology and pathogenesis of cognitive impairment in PSP, as in other degenerative movement disorders, are complex and deserve further elucidation as a basis for adequate treatment to improve the quality of life of patients with this fatal disease.
Topics: Humans; Supranuclear Palsy, Progressive; Quality of Life; Parkinsonian Disorders; Parkinson Disease; Neurodegenerative Diseases; Cognitive Dysfunction
PubMed: 36862189
DOI: 10.1007/s00702-023-02613-w -
Parkinsonism & Related Disorders Jan 2016Traditionally, the clinical picture of progressive supranuclear palsy (PSP) was defined by early postural instability with falls, supranuclear vertical gaze palsy,... (Review)
Review
Traditionally, the clinical picture of progressive supranuclear palsy (PSP) was defined by early postural instability with falls, supranuclear vertical gaze palsy, symmetric akinesia and rigidity, frontal and subcortical dementia, and pseudobulbar palsy, leading to death after a mean disease duration of approximately six years. A definite diagnosis of PSP depends on neuropathological confirmation. In recent years, clinico-pathological studies have drawn attention to various "atypical" clinical manifestations of PSP. In these, a clinical diagnosis of PSP is delayed or never accomplished. Comprehensive understanding of the natural history of PSP is required to permit an early and accurate diagnosis. Based on current evidence, this review provides an update on the clinical spectrum of PSP.
Topics: Accidental Falls; Animals; Diagnosis, Differential; Humans; Phenotype; Supranuclear Palsy, Progressive
PubMed: 26421392
DOI: 10.1016/j.parkreldis.2015.09.041 -
Current Medicinal Chemistry 2015Progressive supranuclear palsy (PSP) is a progressive tauopathy characterized by supranuclear ophthalmoplegia, pseudobulbar palsy, dysarthria, axial rigidity, frontal... (Review)
Review
Progressive supranuclear palsy (PSP) is a progressive tauopathy characterized by supranuclear ophthalmoplegia, pseudobulbar palsy, dysarthria, axial rigidity, frontal lobe dysfunction, and dementia. The typical pathology includes neuronal loss, gliosis and microtubule-associated protein tau (MAPT)-positive inclusions in neurons and glial cells, primarily in basal ganglia, brainstem and cerebellum. The pathogenesis of PSP is not yet completely understood; however, there are several hypotheses. This article reviews the present knowledge about PSP, and the concepts underlying mitochondrial dysfunction, lipoperoxidation, and gene mutations. The clinical features of PSP are also discussed; these include vertical gaze palsy, pseudobulbar palsy, aphasia, dysarthria, axial rigidity, and neuropsychiatric symptoms, such as amnesia, irritability, loss of interest, and dementia. In terms of diagnosis, there is considerable interest in neuroimaging for detecting PSP; therefore, neuroimaging techniques such as magnetic resonance imaging (MRI) and [18F]- fluorodeoxyglucose positron-emission tomography (FDG-PET) are reviewed. A definitive diagnosis of PSP depends on pathology, and the introduction of new clinical subtypes challenges presents the widely adopted diagnosis criteria. PSP treatments such as serotonin antagonists, α2 receptor antagonists, and coenzyme Q10 are also discussed. There is no curative therapy for PSP; all of the available treatments are palliative.
Topics: Humans; Supranuclear Palsy, Progressive
PubMed: 25732053
DOI: 10.2174/0929867322666150302170552 -
Aging Brain 2021Amyotrophic Lateral Sclerosis (ALS) belongs to the family of neurodegenerative disorders and is classified as fronto-temporal dementia (FTD), progressive muscular... (Review)
Review
Amyotrophic Lateral Sclerosis (ALS) belongs to the family of neurodegenerative disorders and is classified as fronto-temporal dementia (FTD), progressive muscular atrophy, primary lateral sclerosis, and pseudobulbar palsy. Even though endocrine dysfunction independently impacts the ALS-related survival rate, the complex connection between ALS and the endocrine system has not been studied in depth. Here we review earlier and recent findings on how ALS interacts with hormones of the hypothalamus and pituitary gland, the thyroid gland, the pancreas, d) the adipose tissue, e) the parathyroid glands, f) the bones, g) the adrenal glands, and the gonads (ovaries and testes). Of note, endocrine issues should always be explored in patients with ALS, especially those with low skeletal muscle and bone mass, vitamin D deficiency, and decreased insulin sensitivity (diabetes mellitus). Because ALS is a progressively deteriorating disease, addressing any potential endocrine co-morbidities in patients with this malady is quite important for decreasing the overall ALS-associated disease burden. Importantly, as this burden is estimated to increase globally in the decades to follow, in part because of an increasingly aging population, it is high time for future multi-center, multi-ethnic studies to assess the link between ALS and the endocrine system in significantly larger patient populations. Last, the psychosocial stress experienced by patients with ALS and its psycho-neuro-endocrinological sequelae, including hypothalamic-pituitaryadrenal dysregulation, should become an area of intensive study in the future.
PubMed: 36911507
DOI: 10.1016/j.nbas.2021.100024 -
Journal of Neurology, Neurosurgery, and... Oct 2017Pseudobulbar affect (PBA) is prevalent in amyotrophic lateral sclerosis (ALS), but there is limited information on its associations and course. (Observational Study)
Observational Study
BACKGROUND
Pseudobulbar affect (PBA) is prevalent in amyotrophic lateral sclerosis (ALS), but there is limited information on its associations and course.
OBJECTIVES
Explore prevalence, associations, course and manifestations of PBA in outpatient cohort of patients with ALS and examine its relationship to depression.
METHODS
Self-reported measures of PBA and depression (Center for Neurologic Study-Lability Scale (CNS-LS) and Patient Health Questionnaire (PHQ-9), respectively) were obtained from consecutive patients with ALS using tablet devices in waiting rooms (Knowledge Program).
RESULTS
PBA (CNS-LS ≥13) was seen in 209/735 patients (28.4%). PBA was associated with bulbar onset and dysfunction, upper motor neuron dysfunction, cognitive impairment, depression and lower quality of life. A multivariable model that included lower bulbar and gross motor subscores, female gender, younger age and shorter duration of disease predicted PBA with 74% accuracy. CNS-LS scores increased only slowly with time. Women with PBA reported more crying than men. Crying (but not laughter) correlated with depression, and crying was associated with poorer quality of life. Exploratory factor analysis of pooled questions of CNS-LS and PHQ-9 identified three underlying factors (laughter, crying and depression) loaded on appropriate questions of the respective instruments.
CONCLUSION
This study identifies associations of PBA and additionally finds PBA (especially crying-predominant PBA) more prevalent in women with ALS. Although the two self-report instruments (CNS-LS and PHQ-9) discriminate well between PBA and depression, there is significant overlap between depression and crying in PBA. Studies of PBA should stratify for gender, examine crying and laughter as separate outcomes and adjust for depression.
Topics: Age Factors; Amyotrophic Lateral Sclerosis; Crying; Depression; Female; Humans; Laughter; Male; Middle Aged; Prevalence; Pseudobulbar Palsy; Quality of Life; Sex Factors; Surveys and Questionnaires
PubMed: 28572273
DOI: 10.1136/jnnp-2017-315622 -
Diagnostics (Basel, Switzerland) Nov 2023The term "Osmotic Demyelination Syndrome" (ODS) is synonymous with central pontine myelinolysis (CPM), denoting a condition characterised by brain damage, particularly...
The term "Osmotic Demyelination Syndrome" (ODS) is synonymous with central pontine myelinolysis (CPM), denoting a condition characterised by brain damage, particularly affecting the white matter tracts of the pontine region. This damage arises due to the rapid correction of metabolic imbalances, primarily cases of hyponatremia. Noteworthy triggers encompass severe burns, liver transplantations, anorexia nervosa, hyperemesis gravidarum, and hyperglycaemia, all linked to the development of CPM. Clinical manifestations encompass a spectrum of signs and symptoms, including dysphagia, dysarthria, spastic quadriparesis, pseudobulbar paralysis, ataxia, lethargy, tremors, disorientation, catatonia, and, in severe instances, locked-in syndrome and coma. A recent case involving a 45-year-old woman illustrates these complexities. Upon admission to the Medicine Intensive Care Unit, she presented with symptoms indicative of diminished responsiveness and bilateral weakness in the upper and lower limbs. Of significance, the patient had a pre-existing medical history of hyperthyroidism. Extensive diagnostic investigations were undertaken, revealing compelling evidence of profound hyponatremia through blood analyses. Furthermore, magnetic resonance imaging (MRI) was performed, unveiling conspicuous areas of abnormal hyperintensity located in the central pons, intriguingly accompanied by spared peripheral regions. These radiological findings align with the characteristic pattern associated with osmotic demyelination syndrome, illuminating the underlying pathology.
PubMed: 37958289
DOI: 10.3390/diagnostics13213393 -
Molecular Medicine Reports Mar 2022Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy described as a syndrome of postural instability, supranuclear vertical gaze palsy, dysarthria,...
Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy described as a syndrome of postural instability, supranuclear vertical gaze palsy, dysarthria, dystonic rigidity of the neck and trunk, dementia, and pseudobulbar palsy. The clinical diagnosis of PSP is often difficult because there are no established biomarkers, and diagnosis is currently based on clinical and imaging findings. Furthermore, the etiology and pathogenesis of PSP remain unknown. Dysregulation of microRNAs (miRNAs/miRs) has been reported to serve an important role in neurodegenerative diseases. However, the miRNA profiles of patients with PSP are rarely reported. The present study aimed to examine cerebrospinal fluid miRNAs, which are considered to be more sensitive indicators of changes in the brain, to elucidate the pathophysiology of PSP and to establish specific biomarkers for diagnosis. The present study used a microarray chip containing 2,632 miRNAs to examine cerebrospinal fluid miRNA expression levels in 11 patients with PSP aged 68‑82 years. A total of 8 age‑ and sex‑matched controls were also included. A total of 38 miRNAs were significantly upregulated and one miRNA was significantly downregulated in the cerebrospinal fluid of patients with PSP. The patients were divided into two groups based on disease stage (early onset and advanced), and changes in miRNA expression were examined. The miRNAs that were most significantly upregulated or downregulated in the early onset group were miR‑204‑3p, miR‑873‑3p and miR‑6840‑5p. The target genes of these miRNAs were associated with molecules related to the ubiquitin‑proteasome system and autophagy pathway. Furthermore, these miRNAs were found to target genes that have been reported to have epigenetic changes following an epigenome‑wide association study of brain tissues of patients with PSP. This suggested that these miRNAs and genes may have some involvement in the pathogenesis of PSP. However, the sample size of the present study was small; therefore, a greater number of patients with PSP should be examined in future studies.
Topics: Aged; Aged, 80 and over; Biomarkers; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Male; MicroRNAs; Middle Aged; Sensitivity and Specificity; Supranuclear Palsy, Progressive; Syndrome
PubMed: 35039873
DOI: 10.3892/mmr.2022.12604 -
The American Journal of Managed Care Dec 2017Pseudobulbar affect (PBA), despite its prevalence and distinctive symptoms, is widely underrecognized and undertreated. It is characterized by uncontrollable laughing or... (Review)
Review
Pseudobulbar affect (PBA), despite its prevalence and distinctive symptoms, is widely underrecognized and undertreated. It is characterized by uncontrollable laughing or crying that can occur in an exaggerated manner or inappropriately to a given situation or stimuli. PBA is thought to center around preexisting neurological conditions, which include Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, traumatic brain injury, and stroke. The PBA Registry Series trial was created to measure the prevalence of PBA among patients with these underlying neurological conditions. Through greater awareness, recognition, and diagnosis, treatment for patients with PBA can be improved.
Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; Female; Humans; Male; Middle Aged; Nervous System Diseases; Parkinson Disease; Prevalence; Pseudobulbar Palsy; Quality of Life; Risk Assessment; Severity of Illness Index; United States
PubMed: 29297656
DOI: No ID Found